Cancer Medicine (Nov 2024)

Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

  • Motohide Uemura,
  • Hiroaki Kikukawa,
  • Yasuhiro Hashimoto,
  • Hiroji Uemura,
  • Atsushi Mizokami,
  • Masashi Kato,
  • Hisashi Matsushima,
  • Takeo Kosaka,
  • Motonobu Nakamura,
  • Satoshi Fukasawa,
  • Matthew R. Smith,
  • Bertrand Tombal,
  • Maha Hussain,
  • Fred Saad,
  • Karim Fizazi,
  • Cora N. Sternberg,
  • E. David Crawford,
  • Haruka Kakiuchi,
  • Masanao Akiyama,
  • Rui Li,
  • Iris Kuss,
  • Heikki Joensuu,
  • Hiroyoshi Suzuki

DOI
https://doi.org/10.1002/cam4.70029
Journal volume & issue
Vol. 13, no. 21
pp. n/a – n/a

Abstract

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Abstract Background In the global ARASENS study (NCT02799602), darolutamide plus androgen‐deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone‐sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants. Methods Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival. Results The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50–1.64), despite 85% of patients in the placebo group receiving subsequent life‐prolonging therapy. Darolutamide prolonged time to castration‐resistant prostate cancer (HR 0.31; 95% CI 0.17–0.55). Treatment‐emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population. Conclusion In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

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